UniProtKB - A2RUS2 (DEND3_HUMAN)
Protein
DENN domain-containing protein 3
Gene
DENND3
Organism
Homo sapiens (Human)
Status
Functioni
Guanine nucleotide exchange factor (GEF) activating RAB12. Promotes the exchange of GDP to GTP, converting inactive GDP-bound RAB12 into its active GTP-bound form (PubMed:20937701). Regulates autophagy in response to starvation through RAB12 activation. Starvation leads to ULK1/2-dependent phosphorylation of Ser-472 and Ser-490, which in turn allows recruitment of 14-3-3 adapter proteins and leads to up-regulation of GEF activity towards RAB12 (By similarity). Also plays a role in protein transport from recycling endosomes to lysosomes, regulating, for instance, the degradation of the transferrin receptor and of the amino acid transporter PAT4 (PubMed:20937701). Starvation also induces phosphorylation at Tyr-858, which leads to up-regulated GEF activity and initiates autophagy (By similarity).By similarity1 Publication
GO - Molecular functioni
- guanyl-nucleotide exchange factor activity Source: UniProtKB
GO - Biological processi
- cellular protein catabolic process Source: UniProtKB
- endosome to lysosome transport Source: UniProtKB
- regulation of Rab protein signal transduction Source: GO_Central
Keywordsi
Molecular function | Guanine-nucleotide releasing factor |
Enzyme and pathway databases
PathwayCommonsi | A2RUS2 |
Reactomei | R-HSA-8876198, RAB GEFs exchange GTP for GDP on RABs |
SignaLinki | A2RUS2 |
Names & Taxonomyi
Protein namesi | Recommended name: DENN domain-containing protein 3 |
Gene namesi | Name:DENND3 Synonyms:KIAA0870 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:29134, DENND3 |
MIMi | 617503, gene |
neXtProti | NX_A2RUS2 |
VEuPathDBi | HostDB:ENSG00000105339.10 |
Subcellular locationi
Cytoplasm and Cytosol
- Cytoplasm By similarity
Note: Transiently recruited to membranes to activate RAB12.By similarity
Cytosol
- cytosol Source: Reactome
Other locations
- cytoplasmic vesicle Source: GO_Central
Keywords - Cellular componenti
CytoplasmPathology & Biotechi
Organism-specific databases
DisGeNETi | 22898 |
OpenTargetsi | ENSG00000105339 |
PharmGKBi | PA142671987 |
Miscellaneous databases
Pharosi | A2RUS2, Tbio |
Genetic variation databases
BioMutai | DENND3 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000304672 | 1 – 1198 | DENN domain-containing protein 3Add BLAST | 1198 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 472 | Phosphoserine; by ULK1By similarity | 1 | |
Modified residuei | 490 | Phosphoserine; by ULK1By similarity | 1 | |
Modified residuei | 858 | PhosphotyrosineBy similarity | 1 |
Keywords - PTMi
PhosphoproteinProteomic databases
EPDi | A2RUS2 |
jPOSTi | A2RUS2 |
MassIVEi | A2RUS2 |
MaxQBi | A2RUS2 |
PaxDbi | A2RUS2 |
PeptideAtlasi | A2RUS2 |
PRIDEi | A2RUS2 |
ProteomicsDBi | 519 [A2RUS2-1] 520 [A2RUS2-2] 521 [A2RUS2-3] 522 [A2RUS2-4] |
PTM databases
iPTMneti | A2RUS2 |
PhosphoSitePlusi | A2RUS2 |
Expressioni
Gene expression databases
Bgeei | ENSG00000105339, Expressed in right lung and 204 other tissues |
ExpressionAtlasi | A2RUS2, baseline and differential |
Genevisiblei | A2RUS2, HS |
Organism-specific databases
HPAi | ENSG00000105339, Tissue enhanced (bone) |
Interactioni
Subunit structurei
Forms oligomers.
Interacts with 6 of the 7 known isoforms of 14-3-3 proteins.
By similarityProtein-protein interaction databases
BioGRIDi | 116562, 3 interactors |
IntActi | A2RUS2, 8 interactors |
STRINGi | 9606.ENSP00000262585 |
Miscellaneous databases
RNActi | A2RUS2, protein |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 1 – 163 | uDENNPROSITE-ProRule annotationAdd BLAST | 163 | |
Domaini | 186 – 318 | cDENNPROSITE-ProRule annotationAdd BLAST | 133 | |
Domaini | 320 – 424 | dDENNPROSITE-ProRule annotationAdd BLAST | 105 | |
Repeati | 893 – 931 | WD 1Sequence analysisAdd BLAST | 39 | |
Repeati | 937 – 973 | WD 2Sequence analysisAdd BLAST | 37 | |
Repeati | 977 – 1018 | WD 3Sequence analysisAdd BLAST | 42 | |
Repeati | 1022 – 1059 | WD 4Sequence analysisAdd BLAST | 38 | |
Repeati | 1065 – 1105 | WD 5Sequence analysisAdd BLAST | 41 | |
Repeati | 1110 – 1152 | WD 6Sequence analysisAdd BLAST | 43 | |
Repeati | 1158 – 1197 | WD 7Sequence analysisAdd BLAST | 40 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 438 – 888 | LinkerCuratedAdd BLAST | 451 |
Domaini
Inactive DENND3 is found in a closed conformation, in which the linker region interacts with the DENN domain. Phosphorylation of Tyr-858 in the linker region intereferes with this interaction leading to an open conformation and enhances the GEF activity of the protein towards RAB12.By similarity
Keywords - Domaini
Repeat, WD repeatPhylogenomic databases
eggNOGi | KOG2127, Eukaryota |
GeneTreei | ENSGT00940000155784 |
HOGENOMi | CLU_280008_0_0_1 |
InParanoidi | A2RUS2 |
OrthoDBi | 521943at2759 |
PhylomeDBi | A2RUS2 |
TreeFami | TF331814 |
Family and domain databases
Gene3Di | 2.130.10.10, 1 hit 3.40.50.11500, 1 hit |
InterProi | View protein in InterPro IPR001194, cDENN_dom IPR005112, dDENN_dom IPR043153, DENN_C IPR037516, Tripartite_DENN IPR015943, WD40/YVTN_repeat-like_dom_sf IPR001680, WD40_repeat IPR019775, WD40_repeat_CS IPR017986, WD40_repeat_dom IPR036322, WD40_repeat_dom_sf |
Pfami | View protein in Pfam PF02141, DENN, 1 hit |
SMARTi | View protein in SMART SM00801, dDENN, 1 hit SM00799, DENN, 1 hit SM00320, WD40, 3 hits |
SUPFAMi | SSF50978, SSF50978, 1 hit |
PROSITEi | View protein in PROSITE PS50211, DENN, 1 hit PS00678, WD_REPEATS_1, 1 hit PS50294, WD_REPEATS_REGION, 1 hit |
s (4+)i Sequence
Sequence statusi: Complete.
This entry describes 4 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 4 described isoforms and 11 potential isoforms that are computationally mapped.Show allAlign All
Isoform 1 (identifier: A2RUS2-1) [UniParc]FASTAAdd to basket
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MRSLRKKREK PRPEQWKGLP GPPRAPEPED VAVPGGVDLL TLPQLCFPGG
60 70 80 90 100
VCVATEPKED CVHFLVLTDV CGNRTYGVVA QYYRPLHDEY CFYNGKTHRE
110 120 130 140 150
CPGCFVPFAV CVVSRFPYYN SLKDCLSCLL ALLKPCKDFE VDSHIKDFAA
160 170 180 190 200
KLSLIPSPPP GPLHLVFNMK SLQIVLPARA DPESPILDLD LHLPLLCFRP
210 220 230 240 250
EKVLQILTCI LTEQRIVFFS SDWALLTLVT ECFMAYLYPL QWQHPFVPIL
260 270 280 290 300
SDQMLDFVMA PTSFLMGCHL DHFEEVSKEA DGLVLINIDH GSITYSKSTD
310 320 330 340 350
DNVDIPDVPL LAAQTFIQRV QSLQLHHELH AAHLLSSTDL KEGRAHRRSW
360 370 380 390 400
QQKLNCQIQQ TTLQLLVSIF RDVKNHLNYE HRVFNSEEFL KTRAPGDHQF
410 420 430 440 450
YKQVLDTYMF HSFLKARLNR RMDAFAQMDL DTQSEEDRIN GMLLSPRRPT
460 470 480 490 500
VEKRASRKSS HLHVTHRRMV VSMPNLQDIA MPELAPRNSS LRLTDTAGCR
510 520 530 540 550
GSSAVLNVTP KSPYTFKIPE IHFPLESKCV QAYHAHFVSM LSEAMCFLAP
560 570 580 590 600
DNSLLLARYL YLRGLVYLMQ GQLLNALLDF QNLYKTDIRI FPTDLVKRTV
610 620 630 640 650
ESMSAPEWEG AEQAPELMRL ISEILDKPHE ASKLDDHVKK FKLPKKHMQL
660 670 680 690 700
GDFMKRVQES GIVKDASIIH RLFEALTVGQ EKQIDPETFK DFYNCWKETE
710 720 730 740 750
AEAQEVSLPW LVMEHLDKNE CVCKLSSSVK TNLGVGKIAM TQKRLFLLTE
760 770 780 790 800
GRPGYLEIST FRNIEEVRRT TTTFLLRRIP TLKIRVASKK EVFEANLKTE
810 820 830 840 850
CDLWHLMVKE MWAGKKLADD HKDPHYVQQA LTNVLLMDAV VGTLQSPGAI
860 870 880 890 900
YAASKLSYFD KMSNEMPMTL PETTLETLKH KINPSAGEAF PQAVDVLLYT
910 920 930 940 950
PGHLDPAEKV EDAHPKLWCA LSEGKVTVFN ASSWTIHQHS FKVGTAKVNC
960 970 980 990 1000
MVMADQNQVW VGSEDSVIYI INVHSMSCNK QLTAHCSSVT DLIVQDGQEA
1010 1020 1030 1040 1050
PSNVYSCSMD GMVLVWNVST LQVTSRFQLP RGGLTSIRLH GGRLWCCTGN
1060 1070 1080 1090 1100
SIMVMKMNGS LHQELKIEEN FKDTSTSFLA FQLLPEEEQL WAACAGRSEV
1110 1120 1130 1140 1150
YIWSLKDLAQ PPQRVPLEDC SEINCMIRVK KQVWVGSRGL GQGTPKGKIY
1160 1170 1180 1190
VIDAERKTVE KELVAHMDTV RTLCSAEDRY VLSGSGREEG KVAIWKGE
Computationally mapped potential isoform sequencesi
There are 11 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketE9PF32 | E9PF32_HUMAN | DENN domain-containing protein 3 | DENND3 | 1,278 | Annotation score: | ||
H0YAY3 | H0YAY3_HUMAN | DENN domain-containing protein 3 | DENND3 | 1,203 | Annotation score: | ||
E5RHH2 | E5RHH2_HUMAN | DENN domain-containing protein 3 | DENND3 | 280 | Annotation score: | ||
E5RIR7 | E5RIR7_HUMAN | DENN domain-containing protein 3 | DENND3 | 208 | Annotation score: | ||
E5RI43 | E5RI43_HUMAN | DENN domain-containing protein 3 | DENND3 | 291 | Annotation score: | ||
E5RJ42 | E5RJ42_HUMAN | DENN domain-containing protein 3 | DENND3 | 124 | Annotation score: | ||
H0YAW2 | H0YAW2_HUMAN | DENN domain-containing protein 3 | DENND3 | 102 | Annotation score: | ||
B3KRG7 | B3KRG7_HUMAN | DENN domain-containing protein 3 | DENND3 hCG_20740 | 248 | Annotation score: | ||
H0YBH5 | H0YBH5_HUMAN | DENN domain-containing protein 3 | DENND3 | 122 | Annotation score: | ||
H0YBK9 | H0YBK9_HUMAN | DENN domain-containing protein 3 | DENND3 | 170 | Annotation score: | ||
There is more potential isoformShow all |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_035053 | 143 | S → N. Corresponds to variant dbSNP:rs307761Ensembl. | 1 | |
Natural variantiVAR_035054 | 364 | Q → R. Corresponds to variant dbSNP:rs11997191Ensembl. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_028075 | 1 – 950 | Missing in isoform 3. 1 PublicationAdd BLAST | 950 | |
Alternative sequenceiVSP_028077 | 128 | C → W in isoform 4. 1 Publication | 1 | |
Alternative sequenceiVSP_028078 | 129 – 1198 | Missing in isoform 4. 1 PublicationAdd BLAST | 1070 | |
Alternative sequenceiVSP_028080 | 319 – 370 | Missing in isoform 2. 1 PublicationAdd BLAST | 52 | |
Alternative sequenceiVSP_028081 | 1133 – 1198 | VWVGS…IWKGE → VGWRARHPQHPRQVSLALAA SPCSREPAARPRALLPSPLR VPLLTGTCRVGANGPTGHHV LVSWCGPSTPQRIPPNWMAS NDRT in isoform 3. 1 PublicationAdd BLAST | 66 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AK058001 mRNA Translation: BAB71630.1 AK131505 mRNA Translation: BAD18649.1 AC040970 Genomic DNA No translation available. BC133023 mRNA Translation: AAI33024.1 BC144226 mRNA Translation: AAI44227.1 AB020677 mRNA Translation: BAA74893.2 |
RefSeqi | NP_055772.2, NM_014957.2 |
Genome annotation databases
Ensembli | ENST00000262585; ENSP00000262585; ENSG00000105339 [A2RUS2-1] ENST00000424248; ENSP00000410594; ENSG00000105339 [A2RUS2-2] |
GeneIDi | 22898 |
KEGGi | hsa:22898 |
UCSCi | uc003yvy.4, human [A2RUS2-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AK058001 mRNA Translation: BAB71630.1 AK131505 mRNA Translation: BAD18649.1 AC040970 Genomic DNA No translation available. BC133023 mRNA Translation: AAI33024.1 BC144226 mRNA Translation: AAI44227.1 AB020677 mRNA Translation: BAA74893.2 |
RefSeqi | NP_055772.2, NM_014957.2 |
3D structure databases
SMRi | A2RUS2 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 116562, 3 interactors |
IntActi | A2RUS2, 8 interactors |
STRINGi | 9606.ENSP00000262585 |
PTM databases
iPTMneti | A2RUS2 |
PhosphoSitePlusi | A2RUS2 |
Genetic variation databases
BioMutai | DENND3 |
Proteomic databases
EPDi | A2RUS2 |
jPOSTi | A2RUS2 |
MassIVEi | A2RUS2 |
MaxQBi | A2RUS2 |
PaxDbi | A2RUS2 |
PeptideAtlasi | A2RUS2 |
PRIDEi | A2RUS2 |
ProteomicsDBi | 519 [A2RUS2-1] 520 [A2RUS2-2] 521 [A2RUS2-3] 522 [A2RUS2-4] |
Protocols and materials databases
Antibodypediai | 27680, 36 antibodies |
Genome annotation databases
Ensembli | ENST00000262585; ENSP00000262585; ENSG00000105339 [A2RUS2-1] ENST00000424248; ENSP00000410594; ENSG00000105339 [A2RUS2-2] |
GeneIDi | 22898 |
KEGGi | hsa:22898 |
UCSCi | uc003yvy.4, human [A2RUS2-1] |
Organism-specific databases
CTDi | 22898 |
DisGeNETi | 22898 |
GeneCardsi | DENND3 |
HGNCi | HGNC:29134, DENND3 |
HPAi | ENSG00000105339, Tissue enhanced (bone) |
MIMi | 617503, gene |
neXtProti | NX_A2RUS2 |
OpenTargetsi | ENSG00000105339 |
PharmGKBi | PA142671987 |
VEuPathDBi | HostDB:ENSG00000105339.10 |
HUGEi | Search... |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG2127, Eukaryota |
GeneTreei | ENSGT00940000155784 |
HOGENOMi | CLU_280008_0_0_1 |
InParanoidi | A2RUS2 |
OrthoDBi | 521943at2759 |
PhylomeDBi | A2RUS2 |
TreeFami | TF331814 |
Enzyme and pathway databases
PathwayCommonsi | A2RUS2 |
Reactomei | R-HSA-8876198, RAB GEFs exchange GTP for GDP on RABs |
SignaLinki | A2RUS2 |
Miscellaneous databases
BioGRID-ORCSi | 22898, 6 hits in 990 CRISPR screens |
ChiTaRSi | DENND3, human |
GenomeRNAii | 22898 |
Pharosi | A2RUS2, Tbio |
PROi | PR:A2RUS2 |
RNActi | A2RUS2, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000105339, Expressed in right lung and 204 other tissues |
ExpressionAtlasi | A2RUS2, baseline and differential |
Genevisiblei | A2RUS2, HS |
Family and domain databases
Gene3Di | 2.130.10.10, 1 hit 3.40.50.11500, 1 hit |
InterProi | View protein in InterPro IPR001194, cDENN_dom IPR005112, dDENN_dom IPR043153, DENN_C IPR037516, Tripartite_DENN IPR015943, WD40/YVTN_repeat-like_dom_sf IPR001680, WD40_repeat IPR019775, WD40_repeat_CS IPR017986, WD40_repeat_dom IPR036322, WD40_repeat_dom_sf |
Pfami | View protein in Pfam PF02141, DENN, 1 hit |
SMARTi | View protein in SMART SM00801, dDENN, 1 hit SM00799, DENN, 1 hit SM00320, WD40, 3 hits |
SUPFAMi | SSF50978, SSF50978, 1 hit |
PROSITEi | View protein in PROSITE PS50211, DENN, 1 hit PS00678, WD_REPEATS_1, 1 hit PS50294, WD_REPEATS_REGION, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | DEND3_HUMAN | |
Accessioni | A2RUS2Primary (citable) accession number: A2RUS2 Secondary accession number(s): B7ZM28 Q96DK3 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | September 11, 2007 |
Last sequence update: | September 11, 2007 | |
Last modified: | April 7, 2021 | |
This is version 123 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- Human chromosome 8
Human chromosome 8: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot